Project Summary/Abstract This proposal aims to optimize country and regional HIV prevention strategies by developing an epidemic economic model of HIV prevention among people who inject drugs (PWID) for 108 countries worldwide using newly available global systematic review data. PWID remain a key risk group for HIV transmission, comprising the majority of new HIV infections in Eastern Europe and Central Asia. Additionally, PWID are important drivers of HIV epidemics in the Middle East and North Africa, and South and South East Asia. Even in countries with generalized HIV epidemics, PWID frequently have an elevated burden of infection and poor access to prevention interventions, creating disparities which limit the ability to achieve the UNAIDS target to reduce HIV incidence by 90% by 2030. Governments lack guidance on the most effective and cost-effective intervention portfolio to prevent HIV among PWID. Newly available and on-going global systematic review data compiled by our team provides important new data to address this question. Our overarching aim is to optimize HIV prevention policymaking for PWID using dynamic economic modeling informed by multiple large data sources. This proposal incorporates model development, validation, and dissemination, through the following specific aims: 1) Develop an epidemic model to estimate the impact of HIV prevention portfolios among PWID for every country with available HIV prevalence data among PWID (108 countries worldwide), based on data from multiple large systematic reviews. 2) Estimate the budgetary impact and cost-effectiveness of the optimal package of interventions for achieving the UNAIDS HIV incidence target among PWID in each country. 3) Externally validate the model in 9 key countries with the highest numbers of HIV-positive PWID. 4) Develop a user-friendly and web-based multi-platform portal for dissemination of the epidemic economic model and associated data. Our team of epidemic modelers, systematic review experts, and drug policy researchers are uniquely poised to utilize these comprehensive new data to provide critical insight into how to tackle HIV epidemics among PWID globally. Our work will have significant impact, guiding policymakers to make informed decisions regarding preventing HIV among this vulnerable group. Our proposal addresses the Office of AIDS Research high priority area of ?reducing the incidence of HIV/AIDS.?